2,4,5-Trioxo-tetrahydro-1,3-oxazines

ABSTRACT

wherein: R1 is hydrogen, optionally branched C1 12 alkyl or 5-membered or 6-membered cycloalkyl, said alkyl being optionally substituted by phenyl which in turn may be unsubstituted or substituted one or more times with fluorine, chlorine, bromine, C1 3 alkyl or trifluoromethyl; in addition to which R1 may represent phenyl or naphthyl which may be unsubstituted or substituted one or more times with C1 3 alkyl or with trifluoromethyl; R2 and R3, which may be identical or different, each is hydrogen, optionally branched C1 18 alkyl or 5-membered or 6membered cycloalkyl, said alkyl being optionally substituted by phenyl which in turn may be unsubstituted or substituted one or more times with fluorine, chlorine, bromine or C1 3 alkyl; and R2 and R3 may also each represent phenyl or naphthyl, unsubstituted or substituted one or more times with fluorine, chlorine, bromine, alkoxy with 1 to 3 C-atoms or alkyl with 1 to 3 C-atoms; and R1 and R2 may also be joined together to form an alkyl bridge having 4 to 6 C-atoms, optionally interrupted by oxygen or sulfur; and R4 represents optionally branched alkyl containing 1 to 6 Catoms or 5-membered or 6-membered cycloalkyl, said alkyl being optionally substituted by phenyl; R4 may also represent phenyl which may be unsubstituted or substituted with fluorine, chlorine, bromine, C1 3 alkyl, trifluoromethyl, alkoxy with 1 to 3 C-atoms or NO2. 2,4,6-TRIOXO-TETRAHYDRO-1,3-OXAZINES HAVING THE FORMULA

[4 1 Oct. 14,1975

[5 4] 2 ,4,6-TRIOXO-TETRAHYDRO-1 ,3-

OXAZINES [75] Inventor: Klaus Grohe,Odenthal-Erberich,

Germany [73] Assignee: Bayer Aktiengesellschaft,

Leverkusen, Germany [22] Filed: Mar. 1, 1974 [21] Appl. No.: 447,406

[30] Foreign Application Priority Data Mar. 9, 1973 Germany 2311708 [52] US. Cl 260/244; 424/248 C071) 265/00; C07D 273/00; 0070 295/00; AOIN 9/00 [51] Int. Cl.

FOREIGN PATENTS OR APPLICATIONS 2,l 37,649 2/1973 Germany Primary Examiner-Albert T. Meyers Assistant Examiner-D. W. Robinson Attorney, Agent, or FirmBurgess, Dinklage & Sprung [5 7] ABSTRACT 2,4,6-trioxo-tetrahydro-1,3-oxazines having the formula wherein:

R is hydrogen, optionally branched C alkyl or 5-membered or 6-membered cycloalkyl, said alkyl being optionally substituted by phenyl which in turn may be unsubstituted or substituted one or more times with fluorine, chlorine, bromine, C alkyl or trifluoromethyl; in addition to which R may represent phenyl or naphthyl which may be unsubstituted or substituted one or more times with C, alkyl or with trifluoromethyl;

R and R which may be identical or different, each is hydrogen, optionally branched C alkyl or 5-membered or 6-membered cycloalkyl, said alkyl being optionally substituted by phenyl which in turn may be unsubstituted or substituted one or more times with fluorine, chlorine, bromine or C alkyl; and R and R may also each represent phenyl or naphthyl, unsubstituted or substituted one or more times with fluorine, chlorine, bromine, alkoxy with l to 3 C-atoms or alkyl with l to 3 C-atoms; and

R and R may also be joined together to form an alkyl bridge having 4 to 6 C-atoms, optionally interrupted by oxygen or sulfur; and

R represents optionally branched alkyl containing 1 to 6 C-atoms or 5-membered or 6-membered cycloalkyl, said alkyl being optionally substituted by phenyl; R may also represent phenyl which may be unsubstituted or substituted with fluorine, chlorine, bromine, C alkyl, trifluoromethyl, alkoxy with 1 to 3 C-atoms or NO;

6 Claims, No Drawings 2,4,5-TRIOXO-TETRAHYDRO-1,3-OXAZINES This invention relates to new 2,4,6-trioxo-tetrahydro- 1,3-oxazines and to a process for preparing them.

SUMMARY It has been found that 2,4,6-trioxo-tetrahydro-1,3- oxazines are obtained when B-aminoacrylic acid esters of the general formula (I):

in which:

R represents a hydrogen atom, an optionally branched C alkyl group or a S-membered or 6- membered cycloalkyl group in which the alkyl groups may be substituted by a phenyl group which in turn may be substituted in one or more positions by fluorine, chlorine, bromine, a C, alkyl group or the trifluoromethyl group; furthermore R may represent a phenyl or naphthyl group which may be substituted in one or more positions by a C alkyl or trifluoromethyl group;

R and R, which may be identical or different, each represents a hydrogen atom, an optionally branched C alkyl group or a S-membered or 6- membered cycloalkyl group, the alkyl groups being optionally substituted by a phenyl group which in turn may be substituted in one or more positions by fluorine, chlorine, bromine or a C alkyl group; and R and R may also represent a phenyl or naphthyl group, which groups may be substituted once or more times by fluorine, chlorine, bromine or an alkoxy group with l to 3 C-atoms or an alkyl group with 1 to 3 C-atoms; and

R and R may also be joined together by an alkylene bridge with 4 to 6 C-atoms which may be interrupted by oxygen or sulphur; and

R may represent an alkyl group with l to 12 C-atoms or a S-membered or 6-membered cycloalkyl group, the alkyl groups being optionally substituted by a phenyl group which in turn may be substituted by fluorine, chlorine, bromine and a C alkyl group,

are reacted with bis-(halocarbonyl)-amines of the formula (II):

COX

COX

in which X denotes a chlorine or bromine atom; and R denotes an optionally branched chain alkyl group containing 1 to 6 C-atoms or a S-membered or 6- membered cycloalkyl group, the alkyl group being optionally substituted by a phenyl group; R may also represent a phenyl group which may be substituted by fluorine, chlorine, bromine, C alkyl, trifluoromethyl, an alkoxy group with l 3 C-atoms or an N group. The new compounds obtainable by the process according to the invention correspond to the following general formula (III):

(III) DESCRIPTION The alkyl groups R -R preferably contain 1 or 2 C- atoms.

It must be regarded as distinctly surprising that the B-aminoacrylic acid esters react with bis- (halocarbonyl)-amines by a process of C,O- cycloacylation to yield the 2,4,6-trioxo-tetrahydrooxazines according to the invention, and do not react by a process involving the basic N-atom, i.e. a process of C,N-cycloacylation to yield pyrimidine diones. Another reason why the process according to this invention is surprising is that B-aminocrotonic acid esters react with chlorocarbonyl sulphenyl chloride by a process of C,N-cycloacylation to form 2 thiazolone-5- carboxylic acid esters (DOS No. 2,137,649).

The preferred B-aminoacrylic acid esters are those in which R represents a methyl or phenyl group, R and R represent hydrogen, an alkyl group containing 1-4 C-atoms, a benzyl or cyclohexyl group or a phenyl group which is optionally substituted with an alkoxy group containing 1 or 2 C-atoms or with chlorine or with an alkyl group containing 1 or 2 C-atoms, and R represents an alkyl group containing l4 C-atoms or a benzyl or cyclohexyl group.

In the bis-(halocarbonyl)-amines, R preferably represents a C to C, all-gyl group, a cyclohexyl group, a benzyl group or a phenyl group which is substituted with chlorine, methoxy, trifluoromethyl, methyl or an N0 group.

The B-aminoacrylic acid esters used as starting material are already known. They can easily be prepared by reacting acylacetoesters with ammonia or primary amines (Organicum, Organische Chem. Grundpraktikum VEB Deutscher Verlag der Wissenschaften, Berlin, page 354 (1964); J. Amer. Chem. Soc. 68, 514 (1946)), by reacting Grignard compounds with cyanoacetates (Collection of Czechoslovak. Chemical Communications 25, 607 (1960)) and by reacting propionic acid esters with ammonia or primary amines (Monatshefte fur Chemie 36, 109 (1915); Chem. Ber. 99, 2526 (I966); Nippon Kagaku Zasshi 82, 632 (1961)).

The following compounds are preferred for the reaction according to the invention: B-aminocrotonic acid methyl. ester, B-arninocrotonic acid ethyl ester, B amiriocrotonic acid i-propyl ester, B-aminocrotonic acid n-dodecyl ester, B-aminocrotonic acid benzyl ester, B-aminocrotonic acid cyclohexyl ester, B-aminocrotonic acid B'-phenethyl ester, B-methylaminocrotonic acid ethyl ester, B-anilinocrotonic acid ethyl ester, B-benzyl-aminocrotonic acid ethyl ester, B-[p-chloroanilino]-crotonic acid ethyl ester, B-aminocinnamic acid ethyl ester, B-amino-B-ethyl acrylic acid ethyl ester, B-methyl-aminocinnamic acid ethyl ester,

, 3,912,730 I ,3 m r I 4 B-dimethyl-aminocrotonic acid methyl ester, I I O B-dimethyl-aminocrotonic acid ethyl ester, B-pyrn s 2 C rolidino-crotomc acid methyl ester, B-piperidinocrotonic acid ethyl ester, B-morpholino-crotonic acid ethyl p1,. CHZl ester, B-dimethyl-aminocinnamic acid methyl'ester and i 0 :0 B-piperidino-cinnamic acid ethyl ester. N Bis-(halocarbonyD-ammes are also known and l readily available. They can easily be obtained by r halogenolytic ring opening of 3,5-dioxo-l,2,4-

dithiazolidines (Synthesis 1970, 564).

The reaction according to the invention of B-aminoacryli acid esters With bis-(halocarbonyl)-amines is for example, prevents the widely spread disease of grey prefer bly rri out at temperatures of from to rot (Botrytis cinerea) when sprayed in a concentration 200C, Particularly to 150C of 0.0025 percent by weight, based on total composi- The B-aminoacrylic acid esters and bisi (halocarbonyl)-amines are generally reacted with each other in a molar ratio of from 1:1 to 1:2; preferably in an inert solvent, with external cooling toithe lower limits of the temperature range until the exothermlc reac- 2O solvent: 4] parts by weight of acetone tion dies down. The reaction is then continued in the Di spersing 0.3 parts by weight of alkyl. upper region of the temperature range until evolution agent: ether Botrytis-Test:

of HCl ceases. The reaction is generally completed water: 95 parts by welghl' after 1 to 4 hours.

The liberated hydrogen chloride y of course, be The quantity of active substance required for obtainbound y one of the bases commonly used for this P!"- ing the desired concentration in the spray liquid is p h as py 0r triethylaminemixed with the specified quantity of solvent, and the The inert solvents u ed f r h pr according to concentrate is diluted with the specified quantity of the invention may be hydrocarbons or chlorinated hywater containing the above mentioned additives. drocarbons, such as benzene, toluene, chlorobenzene, The spray liquid is used to spray young vicia-faba o-dichlorobenzene, carbon tetrachloride, trimethylene 3O sulphone or dioxane.

bean plants, variety Zwijndrechter, which have 3 4 leaf pairs, until they are wet enough to drip.

The process according to the invention will now be After 24 hours, the leaf pairs are removed and the indescribed with the aid of the example of the reaction dividual leaves are placed in petri dishes, the lids and of B-methyl-aminocrotonic acid ethyl ester with bisfloors of which are lined with moist filter paper discs. '(chlorocarbonyl)-methylamine: Filter paper discs 1 cm in diameter are dipped into an Trioxo-tetrahydro-oxazines prepared by this method aqueous spore suspension of botyrris cinerea and then can easily be purified by recrystallisation after the solplaced on the treated leaves in the petri dishes. After vent has been removed by distillation. an incubation period of 48 hours at 20C, the necroses ,7 2,4,6-trioxo-tetrahydro-oxazines .are valuable startvisible under the discs are assessed. ing materials for the synthesis of plant protective agents 50 0 percent means no infection, percent means and may alsobe used directly as fungicides. 5-(1- that the infection is just as high as in control plants. benzylaminoethylidene)-3-methyl-2,4,6-trioxo- The active substance, the concentrations of active tetrahydro-l ,3-oxazine of the formula substance and results are shown in the following table.

Active substance I Infection in 7: of infection of untreated control at a concentration of active substance (in 72) of 0.0025

summarised in the table below were prepared in a manner analogous to that described in Example 1 by reacting 0.3 mol of the corresponding B-aminoacrylic acid ethyl ester with 50 g (0.38 mol) of bis- (chlorocarbonyl)-methylamine in 100 ml of absolute dioxane.

N0. RI R2 R R Yield Mp. Recrystallisation of (C) from theory) 2 CH v H H CH 40 202-203 glacial acetic acid 3 CH3 CH CH;, 65 168-169 toluene 4 CH CH CH CH: 60 178-180 ethanol 5 CH C H CH CH 80 135-136 toluene 6 CH GHQ-Q. on 70 150-151 acetonitrilc 7 C l-1 H CH3 60 189-190 ethanol 8 CH3 H CH;, 70 200-201 acetonitrile 9 CH H CH 65 150-151 ethanol 10 CH, H CH 3 85 172-173 ethanol 11 CH3 CH3 H C8H5 75 167-468 acetonitrile 12 CGHS H H CH" 60 172-173 ethanol 0 EXAMPLE l3 CHFNH g of bis-(chlorocarbonyl)-methylamine are added CH 1 C dropwise to a solution of42.9 g (0.3 mol) of B-methylaminocrotonic acid ethyl ester and 47.4 g (0.3 mol) 0 of pyridine in 100 m1 of absolute dioxane, with cooling melt at 139 to 140C. Yield: 38 g (64 percent of-the theoretical). The same result was obtained when the reaction was carried out in chlorobenzene at-a final temperature of -1 30C;

EXAMPLES2 To 12 The 2,4,6-trioxo-tetrahydro-lQ3-oxazines of the following formula to about 20C and stirring. The reaction mixture is then stirred at room temperature for 30 minutes and at 60C for 45 minutes. 1t is then poured into 250 ml of icewater and the resulting precipitate is suction-filtered and recrystallised from ethanol. Yield: 36 g (60 percent of the theoretical) of the compound of the following ou =c o Mp.: 136 to 138C.

-( l-methylarninoethylidene)'-3-methyl-2,4-6-trioxo EXAMPLE tetrahydro-l,3-oxa zine, 50 g of bis-(chlorocarbonyl)-methylamine are added 5-( l-aminoethylidene)-3-methyl2,4-6-trioxodropwise to a solution of 57.3 g (0.3 mol) of B-aminotetrahydro-l ,3-oxazine; crotonic acid benzyl ester in 100 ml of absolute diox- 5 5-( l-phenylaminoethylidene)-3methyl-2,4,6-trioxoane, with cooling to 40-60C and stirring. The reactetfahydr o-l 3aoxazing; tion mixture is then heated to boiling under reflux until 5 1 i i l mi i -3 ;2 4 evolution of gas ceases. The solvent is then distilled off trioxotetrahydroq 3 under vacuum and the residue is recrystallised from 5 h 3 -g 4 i acetic acid. 35 g of the compound of the following fortetrahydro4 ,3 oxazineil' l 5-(1-p methoxy-phenylaminoethylidene)-3-methyl- 2,4,,6-trioxo-tetrahydrol ,3-oxazine, 5-( l-aminobenzylidene )-3-methyl-2,4,6-trioxotetrahydrol ,3-oxazine, T 5-( l-m-methyl-phenylaminoethylidene)-3-methylu e c 2,4,6-trioxo-tetrahydro-1,3-oxazine,

l 5-( l-o-methyl-phenylaminoethylidene )-3-methyl- 2,4,6-trioxo-tetrahydro-1,3-oxazine, 5-( l-cyclohexylaminoethylidene )-3-methyl-2,4,6- J trioxo-tetrahydro-l ,3-oxazine,

4 I 5-( l -methylaminoethylidene)-3-phenyl-2,4,6-trioxoare obtained. Melting point 200-202C. y -l ,3-0XaZine and S-(a-aminobenzylidene)-3-methyl-2,4,6-trioxo- EXAMPLE tetrahydro-l,3-oxazine.

47.1 g (0.3 mol) of B-aminocrotonic acid n-butyl 3. Process for preparing the 2,4,6-trioxo-tetrahydroester are reacted with 50 g of bis-(chlorocarbonyl)-. l,3-oxazine of claim 1 which comprises reacting methylamine and worked up in a manner analogous to a B-amino-acrylic ester having the formula that described in Example 9. 32 g of the compound of the following formula o N NH: H R' C=CH-COOR Qu -l wherein i R is methyl or phenyl; R and R, which may be the same or different, each is selected from the group I consisting of hydrogen, alkyl containing 1 to 4 C- H atoms, benzyl, cyclohexyl and phenyl which may 40 be optionally substituted by alkoxy or alkyl each with a melting point of 200 202C are obtained. ith 1 or 2 C t m h is C d is; R is alkyl containing 1 to 12 C-atoms or 5-membered l. 2,4,6-trioxo-tetrahydro-l ,3-oxazine having the foror 6-membered cycioaikyi, i alkyl being i mula ally substituted by phenyl optionally substituted by fluorine, chlorine, bromine or C alkyl, with a bis-(halocarbonyl)-amine having the formula wherein L. X is chlorine or bromine, and

- R is selected from the group consisting of C to C h i alkyl, cyclohexyl, benzyl and phenyl R i h l or h l; said B-aminoacrylic acid ester and said bis- R and R, which may be the same or different, each yU- m being c d in molar ratio of is selected from the group consisting of hydrogen, from 1:1 to 122 at a temperature Of from 0 to 200C. alkyl ont inin 1 t 4 C t b l, l h l 6 4. Process ofclai m wherein the temperature is from and phenyl which may be optionally substituted by to 150C alkoxy or alkyl each with 1 or 2 C-atoms; and 5. Process of claim 3 wherein the reaction is carried R is selected from the group consisting of C to C out in the presence of an inert solvent.

alkyl, cyclohexyl, benzyl, and phenyl. 6. Process of claim 3 wherein the reaction is carried 2. The compound of claim 1 selected from the group out in the presence of an acid acceptor. consisting of 

1. 2,4,6,-TRIOXO-TETRALHYDRO-1,3-OXAZINE HAVING THE FORMULA
 2. The compound of claim 1 selected from the group consisting of 5-(1-methylaminoethylidene)-3-methyl-2,4-6-trioxo-tetrahydro-1, 3-oxazine, 5-(1-aminoethylidene)-3-methyl-2,4-6-trioxo-tetrahydro-1,3-oxazine, 5-(1-phenylaminoethylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1, 3-oxazine, 5-(1-dimethylaminoethylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1,3-oxazine, 5-(1-benzylaminoethylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1, 3-oxazine, 5-(1-p-methoxy-phenylaminoethylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1,3 -oxazine, 5-(1-aminobenzylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1,3-oxazine, 5-(1-m-methyl-phenylaminoethylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1,3 -oxazine, 5-(1-o-methyl-phenylaminoethylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1,3 -oxazine, 5-(1-cyclohexylaminoethylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1,3 -oxazine, 5-(1-methylaminoethylidene)-3-phenyl-2,4,6-trioxo-tetrahydro-1, 3-oxazine and 5-( Alpha -aminobenzylidene)-3-methyl-2,4,6-trioxo-tetrahydro-1, 3-oxazine.
 3. Process for preparing the 2,4,6-trioxo-tetrahydro-1,3-oxazine of claim 1 which comprises reacting a Beta -amino-acrylic ester having the formula
 4. Process of claim 3 wherein the temperature is from 30* to 150*C.
 5. Process of claim 3 wherein the reaction is carried out in the presence of an inert solvent.
 6. Process of claim 3 wherein the reaction is carried out in the presence of an acid acceptor. 